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A 3D Human Lung Tissue Model for Functional Studies on Mycobacterium tuberculosis Infection
Published on: October 5, 2015
Diets Differently Regulate Pulmonary Pathogenesis and Immune Signaling in Mice during Acute and Chronic Mycobacterium
Neelam Oswal1, Hariprasad Thangavel1, Kezia Lizardo1
1Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ 07110, USA.
Abstract:
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection persists as a leading cause of mortality and morbidity globally, especially in developing and underdeveloped countries. The prevalence of TB-DM (diabetes mellitus) is higher in low- and middle-income countries where TB and DM are most prevalent. Epidemiological data suggest that slight obesity reduces the risk of TB, whereas DM increases the risk of pulmonary TB. Diets can alter the levels of body fat mass and body mass index by regulating systemic adiposity. Earlier, using a transgenic Mtb-infected murine model, we demonstrated that loss of body fat increased the risk of pulmonary bacterial load and pathology. In the present study, we investigated whether increased adiposity alters pulmonary pathology and bacterial load using C57BL/6 mice infected with HN878 Mtb strain and fed a medium-fat diet (MFD). We analyzed the effects of MFD on the lung during acute and chronic infections by comparing the results to those obtained with infected mice fed a regular diet (RD). Histological and biochemical analyses demonstrated that MFD reduces bacterial burden by increasing the activation of immune cells in the lungs during acute infection and reduces necrosis in the lungs during chronic infection by decreasing lipid accumulation. Our data suggest that slight adiposity likely protects the host during active TB infection by regulating immune and metabolic conditions in the lungs.
Insights
Slight obesity may protect against tuberculosis (TB) by reducing bacterial load and lung damage. Increased adiposity, through a medium-fat diet, enhanced immune responses and decreased pathology in TB-infected mice.
Area of Science:
- Immunology
- Metabolic Diseases
- Infectious Diseases
Background:
- Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a global health crisis, particularly in low- and middle-income countries.
- Diabetes mellitus (DM) exacerbates TB risk, while epidemiological data suggest slight obesity may be protective.
- Diet influences body fat and adiposity, impacting TB susceptibility.
Purpose of the Study:
- To investigate the effect of increased adiposity on pulmonary pathology and bacterial load in a murine model of TB.
- To determine if a medium-fat diet (MFD) alters lung inflammation and Mtb infection outcomes compared to a regular diet (RD).
Main Methods:
- C57BL/6 mice were infected with the HN878 Mtb strain.
- Mice were fed either a medium-fat diet (MFD) or a regular diet (RD).
- Lung tissues were analyzed histologically and biochemically during acute and chronic infection stages.
Main Results:
- MFD reduced bacterial burden during acute infection by enhancing immune cell activation in the lungs.
- MFD decreased lung necrosis during chronic infection by reducing lipid accumulation.
- Slight adiposity, induced by MFD, appears to regulate immune and metabolic conditions in the lungs.
Conclusions:
- Increased adiposity, achieved through a medium-fat diet, demonstrates protective effects against TB in a murine model.
- MFD modulates immune responses and reduces pathological lung damage during both acute and chronic Mtb infection.
- These findings suggest that slight adiposity may play a beneficial role in host defense during active TB infection.
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